Transcription factor AP-2β: A negative regulator of IRS-1 gene expression

摘要: Abstract Down-regulation of insulin receptor substrate-1 (IRS-1) expression could modify the ability IRS-1 to fulfill its functions. It has been proposed that phosphorylation on serine residues promote degradation. However, few studies have investigated transcriptional regulation in pathogenesis resistance. Genotyping for genome-wide single nucleotide polymorphisms revealed transcription factor activating enhancer-binding protein-2β (AP-2β) is a novel candidate gene conferring susceptibility obesity and type 2 diabetes. AP-2β expressed adipose tissue increased during maturation adipocytes. Overexpression leads adipocyte hypertrophy, directly inhibits adiponectin expression, enhanced inflammatory adipokines such as IL-6 MCP-1. In this study, we found overexpression 3T3-L1 adipocytes impaired promoter activity IRS-1, subsequently decreased mRNA protein expression. Electrophoretic mobility shift assays showed bound specifically region. Furthermore, site-directed mutagenesis AP-2 binding site located at −362 −351, relative start site, markedly AP-2-induced suppression activity, whereas other putative sites did not. Our results clearly by promoter. Based these findings, speculate unique regulator